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Acquired immune deficiency syndrome (AIDS) was first discovered in the 1980s, since then, human immunodeficiency virus (HIV) infection and AIDS have become global health, social, and economic concerns. HIV was identified as the cause of AIDS in 1985, and this launched a wide-reaching effort to understand its biology. The knowledge acquired from these vast research efforts contributed to the development of modern therapeutic and preventative treatment strategies. According to recent data from the United Nations Program on HIV/AIDS (UNAIDS), the ratio of infected people to AIDS- related deaths has decreased because of the expanding access to antiretroviral drugs (ARVs). The application of ARVs to HIV+ patients increases patients’ lifespans and improves the quality of life. Remaining as an incurable disease, expanding access to antiretroviral drugs and using prevention strategies are the best options to control the HIV pandemic for now. Treatment strategies with ARVs, however, are not sufficient to adequately address the HIV pandemic. Traditional combinational antiretroviral therapies (cART) for HIV treatment are limited by multiple drawbacks such as possible toxicity, limited drug concentrations, drug resistance, and viral rebound. Additionally, inadequate physicochemical properties of ARVs, such as poor solubility, permeability, and bioavailability, lead to limited absorption and biodistribution, resulting in poor clinical outcomes. Patient compliance and suboptimal efficacy lead to the development of resistant viruses and viral reservoirs. The presence of HIV reservoirs would cause viral rebound two to four weeks after terminating treatments. The complexity of reservoir structure, prolonged cell half-life, and the latent HIV viruses complicate HIV treatments iii targeting viral reservoirs. cART exhibits insufficient efficacy towards reservoir sites because of biological barriers and poor physicochemical properties. These problems highlight an urgent need for novel treatment strategies that are safe and effective to address HIV reservoirs. Innovative and improved delivery systems have been proposed over the years, especially lipid-formulations. Lipid formulations have emerged as promising vehicles owing to their ability to encapsulate molecules with poor solubility and bioavailability, improve active targeting, prolong circulation time, and sustain drug release. Cell-mediated delivery strategy have posed the obstacles of insufficient drug transport and safety. Macrophages, the very same cells that carry the HIV virus, could reach tissues that would otherwise have little or no drug penetration. Macrophages can protect drugs from metabolic degradation with large quantities of drugs for delivery. Activated macrophages express the folate receptor, a potential targeting moiety. In this study, I intended to develop a novel folate-decorated nanoemulsion (FA- NE) for the delivery of ARVs to HIV infected macrophages. To reach the goal, I focused on two goals: (1) construction of a nanocarrier capable of encapsulating ARV drugs with physiological properties suitable for use in drug delivery and (2) enhancement of delivery to HIV infected macrophages. In Chapter 2, I discuss the rationale for nanoART for HIV treatments. I introduce current HIV treatments and their drawbacks, notably the viral rebound due to limited drug concentration in viral reservoirs. Then I explain why nanotechnology would be a promising strategy for HIV treatment and provide examples of nanomedicine. In all iv cases, however, cell uptake and drug release were limited or complicated by toxicity, which is a significant issue for a validated delivery system that are safe and effective. In chapter 3, I introduce the design and development of the FA-NE. This system includes (1) an oil core to encapsulate antiretroviral drugs that are highly hydrophobic, (2) a lipid monolayer to protect the oil core and to form nanoemulsion (3) folate for target. The system was prepared using the emulsification solvent evaporation method, developed and optimized based on physical properties, including size, PDI, zeta potential, and other in vitro characterizations, such as encapsulation efficacy, drug loading, stability, and drug release. Chapter 4 is a continuation of the work done in Chapter 3 and focuses on the enhancement of cellular uptake with folate overexpression cell models. A lipopolysaccharide (LPS) activated macrophages was built and utilized for intracellular drug release and retention evaluations. In Chapter 5, cytotoxicity and antiretroviral efficacy studies are described. With the conclusion drawn in Chapter 4, I was curious if the enhanced cellular uptake can be translated into improved efficacy. As a result, collaborated with Dr. Kamel Khalili, School of Medicine, Temple University, we evaluated antiretroviral efficacy with an HIV indicator cell and monocyte-derived-macrophages from human donors. Furthermore, I performed cytotoxicity assay to evaluate this nanoemulsion system safety profile. Chapter 6 summarizes the highlights and conclusions of this project and provides suggestions for the future. / Pharmaceutical Sciences

Advanced high strength steel (AHSS) provides a lightweight material solution in response to the stringent regulation on fuel economy and greenhouse gas emissions in the automotive industry. Dual phase (DP) steels that consist of a hard martensite phase embedded in a soft ferrite matrix are the most widely used AHSS due to their simple microstructure, robust thermo-mechanical processing and attractive mechanical properties. However, DP steels are prone to deform heterogeneously with strong strain partitioning between phases. The addition of Vanadium in DP steels can form nano-precipitates of vanadium carbonitrides (V (C,N)) that strengthen the ferrite and thus reduce the strain partitioning. This study considered the influence of V (C,N) on the deformation and damage behavior of ferrite-martensite DP1300 steels at the microscopic level. The hardness of the embedded ferrite and martensite regions are determined through nano-hardness testing. In-situ uniaxial tension tests were conducted on DP steels with similar martensite volume fractions within a scanning electron microscope (SEM) chamber. Microscopic-digital image correlation (µDIC) was then employed to analyze the local strain partitioning between ferrite and martensite. Local damage events such as void formation at ferrite martensite island interfaces and in the martensite islands were observed and rationalized with the µDIC results. X-ray computed tomography (XCT) were conducted to quantitatively analyze the microstructure damage. It was found that vanadium addition helps refine the microstructure and improve mechanical compatibility between the two phases. The overall ductility of the steel is enhanced especially in terms of post-uniform elongation and true strain to fracture. / Thesis / Master of Applied Science (MASc)

Yes / To develop high deterioration resistance concrete for marine infrastructures, two types of nano TiO2 (NT) including anatase phase NT and silica surface-treated rutile phase NT were incorporated into concrete. The fabricated NT modified concrete was then put into the marine environment for 21 months in this study. The effects and mechanisms of two types of NT on the deterioration of concrete in the marine environment were investigated from three aspects, including seawater physical and biological and chemical actions on concrete with NT. Under the seawater physical action, the exposed degree of coarse sand particles on the surface of control concrete is greater than that of concrete with NT. Owing to the microorganism biodegradation property of NT, the elimination and inhibition rates of concrete with NT on microorganisms can reach up to 76.98% and 96.81%, respectively. In addition, the surface biofilm thickness of concrete can be reduced by 49.13% due to the inclusion of NT. In the aspect of seawater chemical action, NT can increase the pH value inside concrete by 0.81, increase the degree of polymerization of C-S-H gel, and improve the interfacial transition zone between cement paste and aggregate in concrete. Compared to concrete with anatase phase NT, silica surface-treated rutile phase NT is more effective in improving the deterioration resistance of concrete in the marine environment. It can be concluded that incorporating NT can inhibit the deterioration of concrete in the marine environment.

The use of supercritical carbon dioxide (scCO₂) as a processing aid to help exfoliate nano-clays and improve their dispersion during melt blending in polymer matrices has been reported in the literature. One of the best processes in terms of improving the degree of nano-clay dispersion and composite mechanical properties was developed in our laboratory. This process allows the clay to be in direct contact with scCO₂ and expanding the clay-CO₂ mixture via rapid depressurization into a two-stage screw extruder to mix with the polymer pellets. However, composites with clay loading higher than 6.6 wt % were not reported. In addition, the scCO₂ aided processing method has not been applied to carbon nanotube (CNT) based composites. This dissertation initially focused on applying the scCO₂ aided processing technique to the field of CNT expansion and CNT/polymer composite preparation. The relationship with the expanded CNT morphology and the experimental conditions of the expansion procedure (including pressures, temperatures, exposure time, and depressurization rates) was studied. Microscopy results showed improved CNT dispersion in the polymer matrix and more uniform networks formed with the use of scCO₂, which indicated that CO₂ expanded CNTs are easier to disperse into the polymer matrix during the blending procedure. The CNT/ poly(phenylsulfone) (PPSF) composites prepared with scCO₂ aided method provided continuous improvements in Young's modulus up to the addition of 7 wt % CNTs. However, the Young's modulus of the composite prepared by means of conventional direct melt blending failed to increase beyond the addition of 1 wt % CNT. The second part of this work is concerned with the development of a semi-continuous process using scCO₂ to process polymer-clay composites with clay loading higher than 6.6 wt % (i.e. 10 wt %). Two major modifications are involved in the new procedure: exfoliating the nano-clay directly into the hopper filled with pellets followed by processing the composite immediately and sequentially mixing the clay into the melt. Transmission electron microscopy (TEM) and wide angle X-ray diffraction (WAXD) results show that this modified procedure help to reduce the clay collapse when processing the composites with high clay loadings. Surface modified montmorillonite (MMT) nano-clay/polypropylene (PP) composite at 10 wt % nano-clay with improved clay dispersion was obtained with increased modulus and tensile strength of 63 % and 16%, respectively, compared to the pure PP matrix. Additional mechanical property improvements for nano-clay based composites are then obtained with the use of high crystallinity polypropylene (HCPP) and polypropylene grafted with maleic anhydride (PP-g-MA). HCPP has higher crystallinity and stiffness than conventional PP and, therefore, composites made from HCPP have better mechanical properties to start with. PP-g-MA has polar groups grafted on the PP chains that promote the intercalation of PP with clay. By using the newly developed procedure, the HCPP nanocomposite at 10 wt % of nano-clay has a Young's modulus as high as 3.236 GPa, and the modulus of the 10% MMT/PP-g-MA sample is found to be 2.595 GPa, both higher than that of the composite prepared by the direct blending method and that of a composite based on a conventional PP matrix. / Ph. D.

The thin film pressure balance (TFPB) technique were used to study the stability of single foam films produced in the presence of n-alkyl polyoxyethylene (CnEOm) homologues. The results showed that films thin faster than predicted by the classical DLVO theory, which considers contributions from the van der Waals-dispersion and double-layer forces to the disjoining pressure of the film. The discrepancy may be attributed to the presence of hydrophobic force, the magnitude of which has been estimated using the Reynolds lubrication approximation. It has been found that the attractive hydrophobic force was substantially larger than the attractive van der Waals force, which may explain the faster film thinning kinetics. With a given non-ionic surfactant, the hydrophobic force decreased with increasing surfactant concentration, which explained the slower kinetics observed at higher concentrations and hence the increased foam stability. At concentrations where the hydrophobic force became comparable to or smaller than the van der Waals force, the foam films were stabilized by the increased elasticity of the foam films. The film elasticity of the surfactant solutions were measured using the oscillating drop analysis technique at different frequencies. The measurements were conducted in the presence of CnEOm surfactants with n=10-14 and m=4-8, and the results were analyzed using the Lucassen and van den Tempel model (1972). There was a reasonable fit between the experiment and the model predictions when using the values of the Gibbs elasticity calculated from the Wang and Yoon model (2006). From this exercise, it was possible to determine the diffusion coefficients (D) of the CnEOm surfactants. The D values obtained for CnEOm surfactants were in the range of 2.5x10-10 to 6x10-9 m2s-1, which are in general agreement with those reported in the literature for other surfactants. The diffusion coefficient decreased with increasing alkyl chain length (n) and increased with increasing chain length (m) of the EO group. These findings are in agreement with the results of the dynamic surface tension measurements conducted in the present work. The TFPB studies were also conducted on the foam films stabilized in the presence of a mixture of C12EO8 and sodium dodecylsulfate (SDS) at different ratios. The results showed that the hydrophobic force increased with increasing C12EO8 to SDS ratio. Thus, the former was more effective than the latter in decreasing the hydrophobic force and hence stabilizing foam films. The C12EO8 was more efficient than SDS in increasing the elasticity of the single foam films and stabilizing foams. The TFPB studies were also conducted in the presence of n-octadecyltimethyl chloride (C18TACl) and polymers, i.e., polyvinylpyrrolidone (PVP) and polystyrene sulfonate (PSS). The effect of polymer on the film elasticity was strongest in the presence of PSS, which can be attributed to the charge-charge interaction. Nano-sized silica and poly methyl methacrylate (PMMA) particles were used as solid surfactants to stabilize foams. It was found that the foam stability was maximum at contact angles just below 90o. The TFPB studies conducted with silica nano-particles showed that the kinetics of foam films became slower as the contact angle was increased from 30o to 77 o , indicating that foam films becomes more stable with more hydrophobic particles. The extra-ordinary stability observed with the hydrophobic silica nano-particles may be attributed to the possibility that the particles adsorbed on bubble surfaces retard the drainage rate and prevent the films to reach the critical rupture thickness (Hc). Confocal microscope and SEM images showed that hydrophobized nano-particles adsorbed on the surfaces of air bubbles, and that some of the nano-particles form aggregates depending on the particle size and hydrophobicity. The dynamic surface tension measurements conducted with PMMA and silica nano-particles showed that the latter has higher diffusion rates than the former, which may be due to the differences in particle size and hydrophobicity. / Ph. D.

In recent years, electro-optic polymers have been used to make various optical devices in the telecommunication field due to several advantages, such as large and fast electro-optic (EO) response. Semiconductor nano-crystals promise even higher response speed due to the unique quantum confinement mechanism, and they also show very high EO response because of surface and quantum size effects. Many investigative efforts have been made in the area of semiconductor nano-clusters. These efforts mainly focus on synthesizing high quality particles, and their physical and chemistry properties (luminescence spectra, nonlinear optical, and other effects), but their electro-optic properties and potential uses in devices have not been fully investigated, so there is still much work to do in this aspect. For application of electro-optic polymers in electro-optic devices, the challenges are to develop more stable electro-optic polymers with higher electro-optic coefficients. The electrostatic self-assembly (ESA) technique has many advantages over traditional polymer electro-optic film synthesis processes, such as spin coating. For ESA-generated EO films, no poling field is needed, high orientation of the EO polymer can be obtained which does not degrade with time, so the films can be very stable, and this processing is easily compatible with semiconductor VLSI technology. This is a very attractive technique. The goal of this research is to develop new electro-optic materials by means of ESA techniques and to use them to form improved performance next generation electro-optic devices, with emphasis on two kinds of electro-optic materials: nano-sized II-VI semiconductors (CdS, CdSe), and electro-optic active polymers (chromophores), and their potential use in electro-optic devices. In this research work, II-VI semiconductor nano-clusters have been synthesized, with particle diameters ranging from 4 nm to several tens of nanometers. There is a difference in peak positions of absorption and photo luminescence spectra, related to defects in nano-crystals. Larger CdS particles have larger differences than small CdSe particles. Particle sizes measured by absorption spectrum and by HRTEM methods are very close. Based on quantum mechanical theory, peak spectral shifts as a function of particle size can be predicted, but the theoretical results are typically far from the experimental results, because many complicating factors should be considered. Films fabricated by ESA have much stronger absorption than spin coated films, and exhibit a slight blue shift in peak position wavelength. Photo luminescence spectra also show a blue shift for ESA films with respect to spun films. Polymeric electro-optic films were also fabricated by the ESA technique. Effects due to applying an external electrical field during the ESA process on film growth and properties have also been investigated. Peak position, optical density and wavelength at maximum absorption, all increase with the number of bilayers, and films made under external fields have lower absorption and peak wavelength than those of films fabricated without an external field. These results are related to the order parameter, and indicate that molecule alignment can be improved by the application of an external field during the process of ESA film growth. CdSe nano-clusters have a much higher electro-optic coefficient than their bulk crystal counterparts. In comparison with polymers, they have totally different origins in their electro-optic effects. For both nano-cluster-and chromophore based ESA films, electro-optic coefficients are hi gher than those of spin-coated films, and no poling voltage is needed. The reasons have been fully discussed. This result means that the ESA technique is effective to align and hold the dipoles in films and to intensify the electro-optic effect. CdSe quantum dots need 17. 5 ms to complete their physical orientation due to a rotation of the permanent dipole moment. Therefore, at lower frequencies (<100Hz), electro-optic modulation mainly stems from the orientation of the permanent dipole moment. At frequencies higher than 100 Hz, the electro-optic modulation mainly arises from the induced dipole moment orientation and pure electron movement. The ratio of the electro-optic coefficients r333/r113 > 3. This means that ESA films cannot be treated as an ideal isotropic system with the C v symmetry, and interactions should be considered. Quadratic Kerr electro-optic coefficients have a similar frequency dependence to that of the linear electro-optic coefficients r333 and r113. This indicates that the orientational distribution of the CdSe quantum dots particularly contributes to the quadratic electro-optic modulation. From the FT-IR measurement of the films, proton irradiation can break the N=N double bonding in pi-conjugated bridges, leading to damage of the conjugating structure, so causing a decrease of the EO coefficient. But the thermal and temporal stability of ESA films are much better than those of spin coated films; this is a significant feature of ESA technique. The effect of an external field and film thickness on the optical and electro-optic properties of ESA films has been investigated. Electro-optic coefficient decreases with thickness. Electrical field influences the electronic states of the chromophores. Based on the properties of electro-optic films, the applications of polymer and nano-cluster electro-optic films are discussed. A nano-cluster CdSe electro-optic film has a higher refractive index than the PS-119 polymer film, and these values they are much lower than that of semiconductor wafers, but slightly higher than optical silica glasses. Accordingly optical silica glasses are the ideal substrates for those films. By analysis, the cutoff thickness was determined, which defines the minimum film thickness required for light propagation. For channel waveguides, the aspect ratio w/t, w, and t are determined versus the refractive index of the electro-optic films. Modulator beam length and modulation index were discussed, for high speed operation. Modulator beam length should be carefully chosen to obtain high modulation index; similarly important is the refractive index match between core, substrate, and cladding layers. For high speed operation, traveling wave electrode designs were considered, based on effective refractive index and impedance matching. The effective dielectric constant and characteristic impedance as a function of electrode configuration (sizes) were diagramed, and this served as a basic design suggestion for traveling wave electrodes. / Ph. D.

Surface chemistry of wood is based on the exposed cut surface that is the combination of intact (lumen wall) and cut cell wall material. It is inherently complex and changes with history of processing. Modification of wood surface through noncovalent attachment of amine containing water soluble polyelectrolytes provides a path to create functional surfaces in a controlled manner. Furthermore, modification of the surface can be performed using layer-by-layer (LbL) assembly, where the adsorption of polyelectrolytes or nanoparticles in sequential steps yields a multilayer film with a defined layer sequence on a given substrate. The objective of this study was to quantify adsorption of polyelectrolytes onto wood surface and use these polyelectrolytes as adhesives. In this study, optimal pH conditions for modifying wood surfaces, by anchoring adsorbing polyelectrolytes, were detected using zeta- ( )-potential measurements. Positively charged wood surfaces were also detected by the same technique after a layer of poly(diallyldimethylammonium chloride) (PDDA) or poly (ethylenimine) (PEI) was adsorbed. Both X-ray photoelectron spectroscopy (XPS) and Carbon-Nitrogen-Sulfur analyzer (CNS) were used to quantify the amount of charged polymer on wood surfaces to elucidate optimal pH and ionic strength for polyelectrolyte adsorption. Confocal laser scanning microscopy (CLSM) and Environmental Scanning Electron Microscope (ESEM) were used to characterize adsorbed LbL multilayers of poly(acrylic) acid (PAA) and poly(allylamine hydrochloride) (PAH). Cross-linking between PAA and PAH at various temperatures was studied by Fourier Transform Infrared Spectroscopy (FTIR) and the evaluation of multilayer as bonding agents was carried out by compression shear test following ASTM D905 standard. / Master of Science

Although it is known that gold (Au) is diamagnetic in bulk form, it has been reported that Au displays magnetic properties when reduced to the nano-scale. Researchers found magnetism in Au nanoparticles (NPs) in a size range from 2 to 10 nanometers. Moreover, the Au nanoparticles are usually coated by thiol-containing organic caps, which are believed to be responsible for the magnetism. However, others suggest that organic capping is not necessary to observe magnetism in Au NPs, and magnetism may be an intrinsic property for nano-structured gold. For this investigation, we used pulsed laser deposition to prepare nano-structured gold of different sizes and concentrations to investigate the magnetic properties. Our experiment results confirmed that for the samples in which Au is in the metallic state as nanoparticles with ~5 nm diameter, as well as inthe alloy form, bonded with indium, the samples show ferromagnetism when embedded in an Al2O3 matrix without any thiol-containing organic capping. Our results suggest that ferromagnetism is an intrinsic property of Au nano-structures, which means that it is not necessary to incorporate Au-S bonds with organic coatings in order to observe this phenomenon. We believe due to the significant broken symmetry at the surface of the nanoparticles, holes are generated in d bands of the surface Au atoms. These holes are most possibly responsible for ferromagnetism in Au nanoparticles. The realization of magnetism in Au coupled with the lack of clear understanding of its origin makes the investigation of magnetism of diamagnetic metals ripe for further inquiry. / Ph. D.

Yes / Epigallocatechin gallate (EGCG), the main ingredient in green tea, holds promise as a potential treatment for pulmonary arterial hypertension (PAH). However, EGCG has many drawbacks, including stability issues, low bioavailability, and a short half-life. Therefore, the purpose of this research was to develop and optimize an inhalable EGCG nano-liposome formulation aiming to overcome EGCG’s drawbacks by applying a design of experiments strategy. The aerodynamic behaviour of the optimum formulation was determined using the next-generation impactor (NGI), and its effects on the TGF-β pathway were determined using a cell-based reporter assay. The newly formulated inhalable EGCG liposome had an average liposome size of 105 nm, a polydispersity index (PDI) of 0.18, a zeta potential of −25.5 mV, an encapsulation efficiency of 90.5%, and a PDI after one month of 0.19. These results are in complete agreement with the predicted values of the model. Its aerodynamic properties were as follows: the mass median aerodynamic diameter (MMAD) was 4.41 µm, the fine particle fraction (FPF) was 53.46%, and the percentage of particles equal to or less than 3 µm was 34.3%. This demonstrates that the novel EGCG liposome has all the properties required to be inhalable, and it is expected to be deposited deeply in the lung. The TGFβ pathway is activated in PAH lungs, and the optimum EGCG nano-liposome inhibits TGFβ signalling in cell-based studies and thus holds promise as a potential treatment for PAH. / This study was supported by Schlumberger Foundation’s faculty for the future in the form of PhD funding awarded to Fatma Haddad.